The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Inhibitory Actions of HERG Currents by the Immunosuppressant Drug Cyclosporin A

  • Lee, Seung-Ho (Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School) ;
  • Hahn, Sang-June (Department of Physiology, Medical Research Center, College of Medicine, The Catholic University of Korea) ;
  • Min, Gye-Sik (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology) ;
  • Kim, Ji-Mok (Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Georgia Health Sciences University) ;
  • Jo, Su-Hyun (Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine) ;
  • Choe, Han (Department of Physiology, Research Institute for Biomacromolecules, University of Ulsan College of Medicine) ;
  • Choi, Bok-Hee (Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School)
  • Received : 2011.08.31
  • Accepted : 2011.10.19
  • Published : 2010.10.30
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Abstract

The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $3.17{\mu}m$ and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.

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References

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